A Study of Ixazomib Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01217957
Collaborator
(none)
65
16
5
86.4
4.1
0
Study Details
Study Description
Brief Summary
The purpose of Phase 1 of this study was to determine the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of oral ixazomib administered in combination with lenalidomide and low-dose dexamethasone in participants with newly diagnosed multiple myeloma (NDMM). The purpose of Phase 2 of this study was to determine the overall response rate (ORR) and further evaluate the tolerability and toxicity of the combination of oral ixazomib, lenalidomide, and low-dose dexamethasone in patients with NDMM.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
The drug being tested in this study is called ixazomib. Ixazomib was being tested to treat people who had newly diagnosed multiple myeloma who had not previously received systemic treatment. This study was conducted in two Phases. Phase 1 looked at side effects and lab results in people who took ixazomib to determine the MTD and RP2D. Phase 2 looked at overall response rates and side effects in people who took ixazomib.
The study enrolled 15 patients in Phase 1 and 50 patients in Phase 2. Participants in Phase 1 were assigned to cohorts and received ixazomib 1.68, 2.23, 2.97, or 3.95 mg/m^2 in addition to dexamethasone 40 mg and lenalidomide 25 mg. Participants in Phase 2 received ixazomib 4.0 mg fixed dose in addition to dexamethasone 40 mg and lenalidomide 25 mg. In both Phases study treatment was administered in 28-day Cycles as follows: ixazomib Days 1, 8 and 15, dexamethasone Days 1, 8, 15 and 22, and lenalidomide 25 mg Days 1 through 21.
This multi-center trial was conducted in the United States. The overall time to participate in this study was 12, 28-day cycles with the option to continue into a maintenance portion in the absence of disease progression or unacceptable toxicity. Participants made multiple visits to the clinic and a final visit 30 days after last dose of study drug for a follow-up assessment.
Study Design
Study Type:
Interventional
Actual Enrollment
:
65 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Form of Ixazomib (MLN9708), a Second-Generation Proteasome Inhibitor, Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Requiring Systemic Treatment
Actual Study Start Date
:
Nov 22, 2010
Actual Primary Completion Date
:
Mar 8, 2013
Actual Study Completion Date
:
Feb 2, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
Drug: Ixazomib
Ixazomib capsules
Other Names:
Drug: Lenalidomide
Lenalidomide capsules
Drug: Dexamethasone
Dexamethasone tablets
|
| Experimental: Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
Drug: Ixazomib
Ixazomib capsules
Other Names:
Drug: Lenalidomide
Lenalidomide capsules
Drug: Dexamethasone
Dexamethasone tablets
|
| Experimental: Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
Drug: Ixazomib
Ixazomib capsules
Other Names:
Drug: Lenalidomide
Lenalidomide capsules
Drug: Dexamethasone
Dexamethasone tablets
|
| Experimental: Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
Drug: Ixazomib
Ixazomib capsules
Other Names:
Drug: Lenalidomide
Lenalidomide capsules
Drug: Dexamethasone
Dexamethasone tablets
|
| Experimental: Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
Drug: Ixazomib
Ixazomib capsules
Other Names:
Drug: Lenalidomide
Lenalidomide capsules
Drug: Dexamethasone
Dexamethasone tablets
|
Outcome Measures
Primary Outcome Measures
- Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)]
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
- Phase 2: Objective Response Rate (ORR) Following Treatment With the Combination Of Oral Ixazomib, Lenalidomide And Low-Dose Dexamethasone [Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days)]
ORR was defined as the percentage of participants with Complete (CR) + Very Good Partial Response (VGPR) assessed by the investigatory using International Myeloma Working Group (IMWG) Criteria. CR=Negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or; 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours.
- Phase 1: Recommended Phase 2 Dose of Ixazomib Given in Combination With Lenalidomide and Low-Dose Dexamethasone [Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)]
RP2D will be determined based on number and type of adverse event and serious adverse events, assessments of clinical laboratory values, neurotoxicity grading, and treatment discontinuation.
- Phase 1: Maximum Tolerated Dose (MTD) of Ixazomib Administered Weekly in Combination With Lenalidomide and Low-Dose Dexamethasone [Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)]
MTD of ixazomib will be determined by assessing adverse events and serious adverse events, clinical laboratory values, neurotoxicity grading, and vital sign measurements.
- Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation [Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days)]
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
Secondary Outcome Measures
- Phase 1: Cmax: Maximum Observed Plasma Concentration for Ixazomib [Cycle 1, Days 1 and 15]
Cmax: Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of ixazomib obtained directly from the plasma concentration-time curve.
- Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib [Cycle 1, Days 1 and 15]
Tmax: Time to reach the first maximum observed plasma concentration (Cmax), equal to time (hours) to Cmax, obtained directly from the plasma concentration-time curve.
- Phase 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib [Cycle 1, Days 1 and 15]
AUC(0-168) is a measure of the area under the plasma concentration-time curve from time 0 to 168 hours postdose for Ixazomib.
- Phase 1: Rac: Accumulation Ratio of Ixazomib [Cycle 1, Day 15]
The accumulation ratio (Rac) was estimated as the ratio of AUC(0-168) on Day 15 to the AUC(0-168) on Day 1. AUC(0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose for ixazomib.
- Phase 1: Emax: Maximum Observed Inhibition of Whole Blood 20S Proteasome [Day 1 predose and at multiple time points (up to 168 hours) postdose and Day 15 predose and at multiple time points (up to 336 hours) postdose]
Emax is the maximum observed inhibition of whole blood 20S proteasome. The pharmacodynamics 20S Proteasome samples were collected and the assays were performed; however, concerns about the third-party laboratory's performance of the blood 20S proteasome activity assay were identified that precluded the ability to confirm the accuracy of the data so no data is reported.
- Phase 1: TEmax: Time to the Maximum Observed Inhibition of Whole Blood 20S Proteasome [Day 1 predose and at multiple time points (up to 168 hours) postdose and Day 15 predose and at multiple time points (up to 336 hours) postdose]
TEmax is the time to the maximum observed inhibition of whole blood 20S proteasome. The pharmacodynamics 20S Proteasome samples were collected and the assays were performed; however, concerns about the third-party laboratory's performance of the blood 20S proteasome activity assay were identified that precluded the ability to confirm the accuracy of the data so no data is reported.
- Phase 2: Time to Progression (TTP) [From the first dose of study treatment to the date of first documented progressive disease (Up to 787 days)]
TTP was measured as the time in months from the first dose of study treatment to the date of the first documented progressive disease (PD).
- Phase 2: Overall Survival (OS) [From the first dose of study treatment to the date of death (up to 787 days)]
OS was measured as the time in months from the first dose of study treatment to the date of death + 1 day.
- Phase 2: Overall Response Rate (ORR) [Up to 787 days]
ORR was defined as the percentage of participants with CR, VGPR and Partial Response (PR) assessed by the investigator using IMWG criteria. CR=Negative immunofixation on the serum and urine + Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. PR=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 90% or to < 200 mg per 24 hours. VGPR= Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours.
- Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) [After Cycles 3, 6 and 9 (Up to 787 days)]
Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR is defined as negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours.
- Phase 2: Percentage of Participants With Complete Response (CR), Stringent Complete Response (sCR), Very Good Partial Response (VGPR), Near Complete Response (nCR), Partial Response (PR) and Minimal Response (MR) [Cycles 3, 6, 9 and 12 (Up to 787 days)]
Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR=Negative immunofixation on the serum and urine + Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. sCR= CR + Normal free light chain (FLC) ratio and Absence of clonal cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to < 200 mg per 24 hours. VGPR= Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. nCR=Positive immunofixation analysis of serum or urine as the only evidence of disease. Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. MR=25% to 49% reduction in serum paraprotein and 50% to 89% reduction in urine light chain excretion for 6 weeks.
- Phase 2: Time to Best Response [Up to 787 days]
Time to Best Response was measured as the time in months from the first dose of study treatment to the date of first documented documentation of a confirmed response of partial response (PR) or better.
- Phase 2: Duration of Response (DOR) [Up to 787 days]
DOR was measured as the time in months from the date of first documentation of a confirmed response (CR + PR+ VGPR) to the date of the first documented disease progression (PD). Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR=negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours.
- Phase 2: Progression Free Survival (PFS) [Up to 787 days]
PFS was measured as the time in months from the first dose of study treatment to the date of the first documented PD or death.
- Phase 2: 1 Year Survival Rate [1 year after first dose of study drug]
1-year survival rate is defined as the percentage of participants still alive at year after the first dose of stud drug.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Each patient must meet all of the following eligibility criteria to be enrolled in the study:
-
Male or female patients 18 years or older
-
Previously untreated multiple myeloma diagnosed according to standard criteria requiring systemic treatment
-
Patients must have measurable disease
-
Nonsecretory multiple myeloma based upon standard M-component criteria (i.e., measurable serum/urine M-component) is not allowed unless the baseline serum free light chain level (Freelite™) is evaluated Patients must meet clinical laboratory criteria as specified in study protocol
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
-
Female and male patients MUST adhere to the guidelines of the lenalidomide pregnancy prevention program
-
Must be able to take concurrent aspirin 325 mg daily
-
Voluntary written consent
Exclusion Criteria
Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
-
Peripheral neuropathy that is greater or equal to Grade 2
-
Female patients who are lactating or pregnant
-
Major surgery or radiotherapy within 14 days before the first dose of study drug
-
Serious infection requiring systemic antibiotic therapy within 14 days before the first dose of study drug
-
Diarrhea greater than Grade 1 based on the National Cancer Institute Common Terminology Criteria for Adverse Events
-
Central nervous system involvement.
-
Evidence of current uncontrolled cardiovascular conditions within the past 6 months
-
Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
-
Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
-
Known gastrointestinal condition that could interfere with swallowing or the oral absorption or tolerance of ixazomib
-
No other prior malignancy within 2 years except nonmelanoma skin cancer or carcinoma in situ of any type if they have undergone complete resection
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic Arizona | Scottsdale | Arizona | United States | 85259 |
| 2 | Cedars Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 3 | Rocky Mountain Cancer Center Rose | Denver | Colorado | United States | 80218 |
| 4 | Cancer Center of Central Connecticut | Southington | Connecticut | United States | 06489 |
| 5 | Mayo Clinic Jacksonville | Jacksonville | Florida | United States | 32224 |
| 6 | Mt Sinai Medical Center | Miami Beach | Florida | United States | 33140 |
| 7 | Emory University | Atlanta | Georgia | United States | 30322 |
| 8 | Harry and Jeannette Weinberg Cancer Center at Franklin Square Hospital | Baltimore | Maryland | United States | 21215 |
| 9 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 10 | Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 11 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 12 | Washington University | Saint Louis | Missouri | United States | 63110 |
| 13 | New York Presbyterian Hospital - Weill-Cornell | New York | New York | United States | 10021 |
| 14 | Sarah Cannon Cancer Center | Nashville | Tennessee | United States | 37203 |
| 15 | W VA University Mary Babb Randolph Cancer Center | Morgantown | West Virginia | United States | 26506 |
| 16 | The Medical College of Wisconsin, Inc. | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01217957
Other Study ID Numbers:
- C16005
- U1111-1176-7340
First Posted:
Oct 8, 2010
Last Update Posted:
Mar 14, 2018
Last Verified:
Mar 1, 2018
Keywords provided by Millennium Pharmaceuticals, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled in the study at 10 investigative sites in the United States from 22 November 2010 to data cut-off 08 March 2013. |
|---|---|
| Pre-assignment Detail | Participants with a diagnosis of multiple myeloma were enrolled in 1 of 4 dose-escalation cohorts ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2 in combination with lenalidomide, and dexamethasone to establish maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D) in Phase 2. 65 participants were enrolled; 15 in phase 1 and 50 in phase 2. |
| Arm/Group Title | Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone |
|---|---|---|---|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
| Period Title: Phase 1 | |||||
| STARTED | 3 | 3 | 6 | 3 | 0 |
| COMPLETED | 2 | 3 | 5 | 2 | 0 |
| NOT COMPLETED | 1 | 0 | 1 | 1 | 0 |
| Period Title: Phase 1 | |||||
| STARTED | 0 | 0 | 0 | 0 | 50 |
| COMPLETED | 0 | 0 | 0 | 0 | 49 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1 :Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | Total of all reporting groups |
| Overall Participants | 3 | 3 | 6 | 3 | 50 | 65 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
62.7
(3.21)
|
72.3
(4.51)
|
63.2
(12.19)
|
64.7
(9.29)
|
64.2
(11.16)
|
64.4
(10.67)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
1
33.3%
|
3
100%
|
3
50%
|
2
66.7%
|
20
40%
|
29
44.6%
|
| Male |
2
66.7%
|
0
0%
|
3
50%
|
1
33.3%
|
30
60%
|
36
55.4%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2%
|
1
1.5%
|
| Not Hispanic or Latino |
3
100%
|
3
100%
|
6
100%
|
3
100%
|
49
98%
|
64
98.5%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||||
| White |
3
100%
|
1
33.3%
|
6
100%
|
0
0%
|
42
84%
|
52
80%
|
| Black or African American |
0
0%
|
2
66.7%
|
0
0%
|
3
100%
|
7
14%
|
12
18.5%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2%
|
1
1.5%
|
| Region of Enrollment (participants) [Number] | ||||||
| United States |
3
100%
|
3
100%
|
6
100%
|
3
100%
|
50
100%
|
65
100%
|
| Region of Enrollment (participants) [Number] | ||||||
| United States |
3
100%
|
3
100%
|
6
100%
|
3
100%
|
50
100%
|
65
100%
|
| Height (cm) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [cm] |
168.9
(12.90)
|
155.4
(3.20)
|
165.9
(10.21)
|
171.1
(8.07)
|
169.4
(11.57)
|
168.5
(11.30)
|
| Weight (kg) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [kg] |
87.43
(12.683)
|
64.93
(16.045)
|
72.82
(14.557)
|
116.63
(25.480)
|
86.13
(17.695)
|
85.39
(19.247)
|
| Body Surface Area (m^2) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [m^2] |
2.024
(0.2180)
|
1.665
(0.1923)
|
1.826
(0.2272)
|
2.348
(0.3050)
|
2.011
(0.2343)
|
1.994
(0.2565)
|
Outcome Measures
| Title | Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability |
|---|---|
| Description | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. |
| Time Frame | Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population was defined as all patients who received at least one dose of any of the 3 study drugs. |
| Arm/Group Title | Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle. for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
| Measure Participants | 3 | 3 | 6 | 3 |
| Any AE |
3
100%
|
3
100%
|
6
100%
|
3
100%
|
| SAE |
2
66.7%
|
3
100%
|
1
16.7%
|
2
66.7%
|
| Title | Phase 2: Objective Response Rate (ORR) Following Treatment With the Combination Of Oral Ixazomib, Lenalidomide And Low-Dose Dexamethasone |
|---|---|
| Description | ORR was defined as the percentage of participants with Complete (CR) + Very Good Partial Response (VGPR) assessed by the investigatory using International Myeloma Working Group (IMWG) Criteria. CR=Negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or; 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. |
| Time Frame | Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the response-evaluable population, defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment, with available data. |
| Arm/Group Title | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23. mg/m^2 in Phase 1. |
| Measure Participants | 49 | 52 |
| Number (95% Confidence Interval) [percentage of participants] |
59
1966.7%
|
62
2066.7%
|
| Title | Phase 1: Recommended Phase 2 Dose of Ixazomib Given in Combination With Lenalidomide and Low-Dose Dexamethasone |
|---|---|
| Description | RP2D will be determined based on number and type of adverse event and serious adverse events, assessments of clinical laboratory values, neurotoxicity grading, and treatment discontinuation. |
| Time Frame | Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Phase 1 participants. |
| Arm/Group Title | Phase 1: Ixazomib + Lenalidomide + Dexamethasone |
|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
| Measure Participants | 15 |
| Number [mg/m^2] |
2.23
|
| Title | Phase 1: Maximum Tolerated Dose (MTD) of Ixazomib Administered Weekly in Combination With Lenalidomide and Low-Dose Dexamethasone |
|---|---|
| Description | MTD of ixazomib will be determined by assessing adverse events and serious adverse events, clinical laboratory values, neurotoxicity grading, and vital sign measurements. |
| Time Frame | Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Phase 1 participants. |
| Arm/Group Title | Phase 1: Ixazomib + Lenalidomide + Dexamethasone |
|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
| Measure Participants | 15 |
| Number [mg/m^2] |
2.97
|
| Title | Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation |
|---|---|
| Description | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. |
| Time Frame | Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population was defined as all patients who received at least one dose of any of the 3 study drugs. |
| Arm/Group Title | Phase 2 :Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1. |
| Measure Participants | 50 | 53 |
| Grade 3 or Higher AEs |
76
2533.3%
|
75
2500%
|
| SAEs |
40
1333.3%
|
43
1433.3%
|
| AEs Resulting in Treatment Discontinuation |
8
266.7%
|
8
266.7%
|
| Title | Phase 1: Cmax: Maximum Observed Plasma Concentration for Ixazomib |
|---|---|
| Description | Cmax: Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of ixazomib obtained directly from the plasma concentration-time curve. |
| Time Frame | Cycle 1, Days 1 and 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic (PK) analysis population, defined as all patients enrolled in the phase 1 portion of the study who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib pharmacokinetic parameters, with available data. |
| Arm/Group Title | Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
| Measure Participants | 2 | 3 | 4 | 2 |
| Day 1 (n=1, 3, 4, 1) |
NA
(NA)
|
22.303
(13.0184)
|
94.779
(34.5442)
|
NA
(NA)
|
| Day 15 (n=2, 3, 4, 1) |
11.999
(NA)
|
31.368
(31.9963)
|
53.517
(22.1412)
|
NA
(NA)
|
| Title | Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib |
|---|---|
| Description | Tmax: Time to reach the first maximum observed plasma concentration (Cmax), equal to time (hours) to Cmax, obtained directly from the plasma concentration-time curve. |
| Time Frame | Cycle 1, Days 1 and 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic (PK) analysis population, defined as all patients enrolled in the phase 1 portion of the study who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib pharmacokinetic parameters, with data available. |
| Arm/Group Title | Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
| Measure Participants | 2 | 3 | 4 | 1 |
| Day 1 (n=1, 3, 4, 1) |
1.020
|
1.520
|
1.060
|
0.250
|
| Day 15 (n=2, 3, 4, 1) |
4.165
|
1.000
|
1.015
|
2.000
|
| Title | Phase 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib |
|---|---|
| Description | AUC(0-168) is a measure of the area under the plasma concentration-time curve from time 0 to 168 hours postdose for Ixazomib. |
| Time Frame | Cycle 1, Days 1 and 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic (PK) analysis population, defined as all patients enrolled in the phase 1 portion of the study who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib pharmacokinetic parameters, with available data. |
| Arm/Group Title | Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
| Measure Participants | 2 | 3 | 4 | 1 |
| Day 1 (n=1, 3, 4, 1) |
NA
(NA)
|
587.667
(350.1861)
|
923.484
(156.2679)
|
NA
(NA)
|
| Day 15 (n=2, 3, 3, 1) |
834.608
(NA)
|
1083.998
(104.0256)
|
1831.324
(262.7420)
|
NA
(NA)
|
| Title | Phase 1: Rac: Accumulation Ratio of Ixazomib |
|---|---|
| Description | The accumulation ratio (Rac) was estimated as the ratio of AUC(0-168) on Day 15 to the AUC(0-168) on Day 1. AUC(0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose for ixazomib. |
| Time Frame | Cycle 1, Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic (PK) analysis population, defined as all patients enrolled in the phase 1 portion of the study who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib pharmacokinetic parameters, with available data. |
| Arm/Group Title | Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
| Measure Participants | 1 | 3 | 3 | 0 |
| Geometric Mean (Standard Deviation) [Ratio] |
NA
(NA)
|
1.849
(0.8359)
|
2.051
(0.6469)
|
| Title | Phase 1: Emax: Maximum Observed Inhibition of Whole Blood 20S Proteasome |
|---|---|
| Description | Emax is the maximum observed inhibition of whole blood 20S proteasome. The pharmacodynamics 20S Proteasome samples were collected and the assays were performed; however, concerns about the third-party laboratory's performance of the blood 20S proteasome activity assay were identified that precluded the ability to confirm the accuracy of the data so no data is reported. |
| Time Frame | Day 1 predose and at multiple time points (up to 168 hours) postdose and Day 15 predose and at multiple time points (up to 336 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Phase 1: TEmax: Time to the Maximum Observed Inhibition of Whole Blood 20S Proteasome |
|---|---|
| Description | TEmax is the time to the maximum observed inhibition of whole blood 20S proteasome. The pharmacodynamics 20S Proteasome samples were collected and the assays were performed; however, concerns about the third-party laboratory's performance of the blood 20S proteasome activity assay were identified that precluded the ability to confirm the accuracy of the data so no data is reported. |
| Time Frame | Day 1 predose and at multiple time points (up to 168 hours) postdose and Day 15 predose and at multiple time points (up to 336 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone |
|---|---|---|---|---|
| Arm/Group Description | In phase 1, ixazomib 1.68 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.23 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 2.97 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 1, ixazomib 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Phase 2: Time to Progression (TTP) |
|---|---|
| Description | TTP was measured as the time in months from the first dose of study treatment to the date of the first documented progressive disease (PD). |
| Time Frame | From the first dose of study treatment to the date of first documented progressive disease (Up to 787 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The modified Intent-to-Treat (mITT) population was defined as all patients who received at least one dose of any study drug in phase 2 or who received at least one dose of any study drug and were treated at the phase 2 dose level during phase 1. |
| Arm/Group Title | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1. |
| Measure Participants | 50 | 53 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | Phase 2: Overall Survival (OS) |
|---|---|
| Description | OS was measured as the time in months from the first dose of study treatment to the date of death + 1 day. |
| Time Frame | From the first dose of study treatment to the date of death (up to 787 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population included al participants who received 1 of the 3 study drugs. Participants who did not die were censored at the last study visit. |
| Arm/Group Title | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1. |
| Measure Participants | 50 | 53 |
| Median (95% Confidence Interval) [participants] |
NA
NaN
|
NA
NaN
|
| Title | Phase 2: Overall Response Rate (ORR) |
|---|---|
| Description | ORR was defined as the percentage of participants with CR, VGPR and Partial Response (PR) assessed by the investigator using IMWG criteria. CR=Negative immunofixation on the serum and urine + Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. PR=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 90% or to < 200 mg per 24 hours. VGPR= Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. |
| Time Frame | Up to 787 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The response-evaluable population was defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment. |
| Arm/Group Title | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1. |
| Measure Participants | 49 | 52 |
| Number (95% Confidence Interval) [percentage of participants] |
88
2933.3%
|
88
2933.3%
|
| Title | Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) |
|---|---|
| Description | Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR is defined as negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. |
| Time Frame | After Cycles 3, 6 and 9 (Up to 787 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The response-evaluable population was defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment. |
| Arm/Group Title | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1. |
| Measure Participants | 49 | 52 |
| After 3 cycles |
35
1166.7%
|
37
1233.3%
|
| After 6 cycles |
47
1566.7%
|
48
1600%
|
| After 9 cycles |
57
1900%
|
58
1933.3%
|
| Title | Phase 2: Percentage of Participants With Complete Response (CR), Stringent Complete Response (sCR), Very Good Partial Response (VGPR), Near Complete Response (nCR), Partial Response (PR) and Minimal Response (MR) |
|---|---|
| Description | Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR=Negative immunofixation on the serum and urine + Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. sCR= CR + Normal free light chain (FLC) ratio and Absence of clonal cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to < 200 mg per 24 hours. VGPR= Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. nCR=Positive immunofixation analysis of serum or urine as the only evidence of disease. Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. MR=25% to 49% reduction in serum paraprotein and 50% to 89% reduction in urine light chain excretion for 6 weeks. |
| Time Frame | Cycles 3, 6, 9 and 12 (Up to 787 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The response-evaluable population was defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment. |
| Arm/Group Title | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1. |
| Measure Participants | 49 | 52 |
| CR |
20
666.7%
|
23
766.7%
|
| sCR |
6
200%
|
10
333.3%
|
| VGPR |
39
1300%
|
38
1266.7%
|
| nCR |
2
66.7%
|
2
66.7%
|
| PR |
67
2233.3%
|
65
2166.7%
|
| MR |
6
200%
|
6
200%
|
| Title | Phase 2: Time to Best Response |
|---|---|
| Description | Time to Best Response was measured as the time in months from the first dose of study treatment to the date of first documented documentation of a confirmed response of partial response (PR) or better. |
| Time Frame | Up to 787 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants form the response-evaluable population, defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment, with available data. |
| Arm/Group Title | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1. |
| Measure Participants | 43 | 46 |
| Median (Full Range) [months] |
2.96
|
3.01
|
| Title | Phase 2: Duration of Response (DOR) |
|---|---|
| Description | DOR was measured as the time in months from the date of first documentation of a confirmed response (CR + PR+ VGPR) to the date of the first documented disease progression (PD). Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR=negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. |
| Time Frame | Up to 787 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the Response Evaluable Population, defined as all patients who received at least one dose of ixazomib, had measurable disease at baseline, and at least one post-baseline disease assessment, with data available for analysis. Patients who did not experience PD were censored at the last response assessment that was SD or better. |
| Arm/Group Title | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1. |
| Measure Participants | 49 | 52 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | Phase 2: Progression Free Survival (PFS) |
|---|---|
| Description | PFS was measured as the time in months from the first dose of study treatment to the date of the first documented PD or death. |
| Time Frame | Up to 787 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mITT population was defined as all patients who received at least one dose of any study drug in phase 2 or who received at least one dose of any study drug and were treated at the phase 2 dose level during phase 1. |
| Arm/Group Title | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Includes 3 participants who received 2.23 mg/m^2 in Phase 1. |
| Measure Participants | 50 | 53 |
| Median (95% Confidence Interval) [months] |
14.98
|
NA
|
| Title | Phase 2: 1 Year Survival Rate |
|---|---|
| Description | 1-year survival rate is defined as the percentage of participants still alive at year after the first dose of stud drug. |
| Time Frame | 1 year after first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone |
|---|---|---|
| Arm/Group Description | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle. for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once, on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once, on Days 1 through 21 of a 28-day cycle. Includes 3 participants who received 2.23 mg/m^2 in Phase 1. |
| Measure Participants | 42 | 45 |
| Number (95% Confidence Interval) [percentage of participants] |
92
3066.7%
|
92
3066.7%
|
Adverse Events
| Time Frame | Up to 787 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||
| Arm/Group Title | Phase 1: Ixazomib + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | ||
| Arm/Group Description | In phase 1, ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68, 2.23, 2.97 or 3.95 mg/m^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. | ||
All Cause Mortality |
||||
| Phase 1: Ixazomib + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Phase 1: Ixazomib + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/15 (53.3%) | 20/50 (40%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/15 (0%) | 1/50 (2%) | ||
| Thrombocytopenia | 0/15 (0%) | 1/50 (2%) | ||
| Cardiac disorders | ||||
| Cardiac failure congestive | 0/15 (0%) | 2/50 (4%) | ||
| Atrial fibrillation | 1/15 (6.7%) | 0/50 (0%) | ||
| Atrial flutter | 0/15 (0%) | 1/50 (2%) | ||
| Angina pectoris | 0/15 (0%) | 1/50 (2%) | ||
| Cardio-respiratory arrest | 0/15 (0%) | 1/50 (2%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 1/15 (6.7%) | 2/50 (4%) | ||
| Nausea | 1/15 (6.7%) | 1/50 (2%) | ||
| Vomiting | 1/15 (6.7%) | 1/50 (2%) | ||
| Constipation | 0/15 (0%) | 1/50 (2%) | ||
| Gastrooesophageal reflux disease | 0/15 (0%) | 1/50 (2%) | ||
| Abdominal hernia | 0/15 (0%) | 1/50 (2%) | ||
| Faecaloma | 0/15 (0%) | 1/50 (2%) | ||
| Intestinal perforation | 0/15 (0%) | 1/50 (2%) | ||
| Gastrointestinal haemorrhage | 1/15 (6.7%) | 0/50 (0%) | ||
| General disorders | ||||
| Asthenia | 1/15 (6.7%) | 1/50 (2%) | ||
| Fatigue | 0/15 (0%) | 1/50 (2%) | ||
| Non-cardiac chest pain | 0/15 (0%) | 2/50 (4%) | ||
| Pyrexia | 1/15 (6.7%) | 0/50 (0%) | ||
| Hernia obstructive | 0/15 (0%) | 1/50 (2%) | ||
| Oedema peripheral | 0/15 (0%) | 1/50 (2%) | ||
| Infections and infestations | ||||
| Pneumonia | 1/15 (6.7%) | 4/50 (8%) | ||
| Diverticulitis | 0/15 (0%) | 1/50 (2%) | ||
| Bone abscess | 0/15 (0%) | 1/50 (2%) | ||
| Postoperative wound infection | 0/15 (0%) | 1/50 (2%) | ||
| Pneumonia respiratory syncytial viral | 0/15 (0%) | 1/50 (2%) | ||
| Sepsis | 0/15 (0%) | 1/50 (2%) | ||
| Injury, poisoning and procedural complications | ||||
| Limb traumatic amputation | 0/15 (0%) | 1/50 (2%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/15 (6.7%) | 3/50 (6%) | ||
| Hypovolaemia | 1/15 (6.7%) | 0/50 (0%) | ||
| Hyponatraemia | 1/15 (6.7%) | 0/50 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/15 (0%) | 3/50 (6%) | ||
| Nervous system disorders | ||||
| Neuropathy peripheral | 1/15 (6.7%) | 0/50 (0%) | ||
| Peripheral sensory neuropathy | 0/15 (0%) | 1/50 (2%) | ||
| Syncope | 1/15 (6.7%) | 0/50 (0%) | ||
| Dizziness | 1/15 (6.7%) | 0/50 (0%) | ||
| Psychiatric disorders | ||||
| Anxiety | 0/15 (0%) | 1/50 (2%) | ||
| Renal and urinary disorders | ||||
| Renal failure acute | 0/15 (0%) | 1/50 (2%) | ||
| Renal failure chronic | 0/15 (0%) | 1/50 (2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 0/15 (0%) | 1/50 (2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash maculo-papular | 1/15 (6.7%) | 0/50 (0%) | ||
| Vascular disorders | ||||
| Hypotension | 1/15 (6.7%) | 1/50 (2%) | ||
| Orthostatic hypotension | 1/15 (6.7%) | 1/50 (2%) | ||
| Deep vein thrombosis | 1/15 (6.7%) | 1/50 (2%) | ||
| Embolism | 0/15 (0%) | 1/50 (2%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Phase 1: Ixazomib + Lenalidomide + Dexamethasone | Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/15 (100%) | 50/50 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Leukopenia | 1/15 (6.7%) | 7/50 (14%) | ||
| Lymphopenia | 3/15 (20%) | 7/50 (14%) | ||
| Neutropenia | 2/15 (13.3%) | 16/50 (32%) | ||
| Cardiac disorders | ||||
| Tachycardia | 1/15 (6.7%) | 5/50 (10%) | ||
| Ear and labyrinth disorders | ||||
| Deafness | 1/15 (6.7%) | 1/50 (2%) | ||
| Tinnitus | 0/15 (0%) | 3/50 (6%) | ||
| Eye disorders | ||||
| Dry eye | 0/15 (0%) | 4/50 (8%) | ||
| Eye pain | 1/15 (6.7%) | 1/50 (2%) | ||
| Vision blurred | 1/15 (6.7%) | 6/50 (12%) | ||
| Visual impairment | 1/15 (6.7%) | 1/50 (2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 2/15 (13.3%) | 1/50 (2%) | ||
| Abdominal distension | 3/15 (20%) | 5/50 (10%) | ||
| Abdominal pain | 1/15 (6.7%) | 4/50 (8%) | ||
| Abdominal pain upper | 1/15 (6.7%) | 3/50 (6%) | ||
| Dry mouth | 0/15 (0%) | 4/50 (8%) | ||
| Dyspepsia | 1/15 (6.7%) | 2/50 (4%) | ||
| Dysphagia | 1/15 (6.7%) | 2/50 (4%) | ||
| Hypoaesthesia oral | 1/15 (6.7%) | 0/50 (0%) | ||
| Melaena | 1/15 (6.7%) | 0/50 (0%) | ||
| Mouth ulceration | 1/15 (6.7%) | 0/50 (0%) | ||
| Oral pain | 1/15 (6.7%) | 0/50 (0%) | ||
| Stomatitis | 1/15 (6.7%) | 4/50 (8%) | ||
| General disorders | ||||
| Chest pain | 1/15 (6.7%) | 0/50 (0%) | ||
| Irritability | 1/15 (6.7%) | 2/50 (4%) | ||
| Local swelling | 1/15 (6.7%) | 0/50 (0%) | ||
| Malaise | 1/15 (6.7%) | 7/50 (14%) | ||
| Pain | 0/15 (0%) | 4/50 (8%) | ||
| Hepatobiliary disorders | ||||
| Cholelithiasis | 1/15 (6.7%) | 0/50 (0%) | ||
| Infections and infestations | ||||
| Cellulitis | 2/15 (13.3%) | 1/50 (2%) | ||
| Folliculitis | 1/15 (6.7%) | 0/50 (0%) | ||
| Fungal skin infection | 1/15 (6.7%) | 1/50 (2%) | ||
| Herpes simplex | 1/15 (6.7%) | 0/50 (0%) | ||
| Nasal vestibulitis | 1/15 (6.7%) | 0/50 (0%) | ||
| Nasopharyngitis | 1/15 (6.7%) | 2/50 (4%) | ||
| Oral herpes | 2/15 (13.3%) | 2/50 (4%) | ||
| Rash pustular | 1/15 (6.7%) | 1/50 (2%) | ||
| Skin infection | 0/15 (0%) | 3/50 (6%) | ||
| Upper respiratory tract infection | 7/15 (46.7%) | 16/50 (32%) | ||
| Urinary tract infection | 0/15 (0%) | 3/50 (6%) | ||
| Injury, poisoning and procedural complications | ||||
| Arthropod bite | 1/15 (6.7%) | 0/50 (0%) | ||
| Fall | 1/15 (6.7%) | 2/50 (4%) | ||
| Sunburn | 1/15 (6.7%) | 0/50 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 0/15 (0%) | 6/50 (12%) | ||
| Aspartate aminotransferase increased | 0/15 (0%) | 4/50 (8%) | ||
| Blood alkaline phosphatase increased | 1/15 (6.7%) | 4/50 (8%) | ||
| Blood creatinine increased | 1/15 (6.7%) | 7/50 (14%) | ||
| Blood lactate dehydrogenase increased | 1/15 (6.7%) | 0/50 (0%) | ||
| Haemoglobin decreased | 1/15 (6.7%) | 0/50 (0%) | ||
| Weight decreased | 2/15 (13.3%) | 3/50 (6%) | ||
| Weight increased | 2/15 (13.3%) | 7/50 (14%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 4/15 (26.7%) | 6/50 (12%) | ||
| Gout | 1/15 (6.7%) | 1/50 (2%) | ||
| Hyperglycaemia | 0/15 (0%) | 3/50 (6%) | ||
| Hypocalcaemia | 0/15 (0%) | 9/50 (18%) | ||
| Hypokalaemia | 4/15 (26.7%) | 9/50 (18%) | ||
| Hypomagnesaemia | 1/15 (6.7%) | 2/50 (4%) | ||
| Hypophosphataemia | 0/15 (0%) | 6/50 (12%) | ||
| Tumour lysis syndrome | 1/15 (6.7%) | 0/50 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 5/15 (33.3%) | 8/50 (16%) | ||
| Bone pain | 2/15 (13.3%) | 5/50 (10%) | ||
| Joint stiffness | 1/15 (6.7%) | 1/50 (2%) | ||
| Muscle spasms | 6/15 (40%) | 9/50 (18%) | ||
| Muscular weakness | 1/15 (6.7%) | 4/50 (8%) | ||
| Musculoskeletal chest pain | 3/15 (20%) | 4/50 (8%) | ||
| Musculoskeletal discomfort | 0/15 (0%) | 3/50 (6%) | ||
| Musculoskeletal pain | 2/15 (13.3%) | 5/50 (10%) | ||
| Myalgia | 1/15 (6.7%) | 5/50 (10%) | ||
| Neck pain | 1/15 (6.7%) | 0/50 (0%) | ||
| Pain in extremity | 4/15 (26.7%) | 11/50 (22%) | ||
| Nervous system disorders | ||||
| Amnesia | 0/15 (0%) | 3/50 (6%) | ||
| Dysgeusia | 3/15 (20%) | 11/50 (22%) | ||
| Headache | 3/15 (20%) | 8/50 (16%) | ||
| Hypoaesthesia | 3/15 (20%) | 3/50 (6%) | ||
| Memory impairment | 1/15 (6.7%) | 1/50 (2%) | ||
| Paraesthesia | 1/15 (6.7%) | 5/50 (10%) | ||
| Sinus headache | 1/15 (6.7%) | 0/50 (0%) | ||
| Tremor | 0/15 (0%) | 5/50 (10%) | ||
| Psychiatric disorders | ||||
| Agitation | 1/15 (6.7%) | 1/50 (2%) | ||
| Confusional state | 1/15 (6.7%) | 0/50 (0%) | ||
| Depression | 1/15 (6.7%) | 3/50 (6%) | ||
| Insomnia | 3/15 (20%) | 18/50 (36%) | ||
| Mental status changes | 1/15 (6.7%) | 1/50 (2%) | ||
| Mood swings | 1/15 (6.7%) | 0/50 (0%) | ||
| Renal and urinary disorders | ||||
| Lower urinary tract symptoms | 1/15 (6.7%) | 0/50 (0%) | ||
| Nocturia | 1/15 (6.7%) | 1/50 (2%) | ||
| Pollakiuria | 1/15 (6.7%) | 2/50 (4%) | ||
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 1/15 (6.7%) | 0/50 (0%) | ||
| Breast tenderness | 1/15 (6.7%) | 0/50 (0%) | ||
| Erectile dysfunction | 1/15 (6.7%) | 1/50 (2%) | ||
| Postmenopausal haemorrhage | 1/15 (6.7%) | 0/50 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 4/15 (26.7%) | 14/50 (28%) | ||
| Dyspnoea exertional | 2/15 (13.3%) | 1/50 (2%) | ||
| Epistaxis | 0/15 (0%) | 5/50 (10%) | ||
| Nasal congestion | 2/15 (13.3%) | 2/50 (4%) | ||
| Oropharyngeal pain | 2/15 (13.3%) | 4/50 (8%) | ||
| Pleural effusion | 1/15 (6.7%) | 0/50 (0%) | ||
| Productive cough | 1/15 (6.7%) | 0/50 (0%) | ||
| Rhinitis allergic | 1/15 (6.7%) | 0/50 (0%) | ||
| Rhinorrhoea | 1/15 (6.7%) | 2/50 (4%) | ||
| Sinus congestion | 0/15 (0%) | 6/50 (12%) | ||
| Wheezing | 1/15 (6.7%) | 0/50 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Acne | 1/15 (6.7%) | 0/50 (0%) | ||
| Alopecia | 1/15 (6.7%) | 0/50 (0%) | ||
| Angioedema | 1/15 (6.7%) | 0/50 (0%) | ||
| Dry skin | 0/15 (0%) | 4/50 (8%) | ||
| Erythema | 1/15 (6.7%) | 3/50 (6%) | ||
| Macule | 1/15 (6.7%) | 0/50 (0%) | ||
| Night sweats | 1/15 (6.7%) | 3/50 (6%) | ||
| Palmar-plantar erythrodysaesthesia syndrome | 1/15 (6.7%) | 0/50 (0%) | ||
| Pruritus | 1/15 (6.7%) | 3/50 (6%) | ||
| Rash | 0/15 (0%) | 4/50 (8%) | ||
| Rash erythematous | 3/15 (20%) | 4/50 (8%) | ||
| Rash macular | 0/15 (0%) | 10/50 (20%) | ||
| Rash papular | 2/15 (13.3%) | 1/50 (2%) | ||
| Rash pruritic | 2/15 (13.3%) | 6/50 (12%) | ||
| Skin exfoliation | 2/15 (13.3%) | 0/50 (0%) | ||
| Skin hyperpigmentation | 0/15 (0%) | 3/50 (6%) | ||
| Skin lesion | 1/15 (6.7%) | 1/50 (2%) | ||
| Skin ulcer | 1/15 (6.7%) | 0/50 (0%) | ||
| Urticaria | 1/15 (6.7%) | 1/50 (2%) | ||
| Vascular disorders | ||||
| Hypertension | 4/15 (26.7%) | 1/50 (2%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
| Name/Title | Medical Director, Clinical Science |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01217957
Other Study ID Numbers:
- C16005
- U1111-1176-7340
First Posted:
Oct 8, 2010
Last Update Posted:
Mar 14, 2018
Last Verified:
Mar 1, 2018